Patent Application
20080033300
Like reference numerals refer to corresponding parts throughout the several views of the drawings.
Radiofrequency ablation (RFA) is used for local tissue ablation. See Decadt and Siriwardena, 2004, “Radiofrequency ablation of liver tumors: systematic review,” Lancet Oncol 5, 550-560, which is hereby incorporated by reference. In RFA, a needle electrode (e.g., 14-17.5 G) with an insulated shaft and a non-insulated distal tip is inserted into or over a lesion, often with imaging-guidance. For example, the physician may be guided in the placement of the needle by images from an imaging provided by ultrasound, a CT scanner, or magnetic resonance. In some procedures, once the needle is in place, tines are deployed from the hollow core of the needle. These tines penetrate the tissue. The patient is made into an electrical circuit by placing grounding pads in appropriate places (e.g. on the thighs or back muscles). RFA energy is then sent through the needle and tines, destroying the tissue.
Radiofrequency ablation is an attractive tool for cancer patients, especially for liver diseases and lung cancer. Since the patient's body is only penetrated with the needle in such procedures, RFA is minimally invasive. Some patients are able to return home the day of the procedure while others are observed overnight. Because the procedure is minimally invasive, patients can begin, or continue with, chemotherapy. In addition, the needle can be placed in locations unavailable to surgery, so that many tumors can be destroyed which would otherwise be inoperable. While RFA has previously been used to ablate small tumors, multiple placements of the needle can effectively ablate larger tumors as well. Even if all of the large tumor cannot be ablated, there is much to be gained from the debulking of a large tumor.
Radiofrequency ablation has also proven to be an effective and curative treatment for heart ailments including several supraventricular and ventricular tachyarrhythmias. RFA has been used for clinical applications such as osteiod osteoma, nerve ganglion ablation, and dermatological treatment. For instance, U.S. Pat. No. 7,020,528, which is hereby incorporated by reference herein in its entirety, provides a method for treatment of acne using RFA.
One drawback of RFA is the “heat-sink” effect. The heat-sink effect may occur in treated tissue adjacent to large vessels. The inflow of “cool” blood at body temperature (cool relative to the ablation temperatures) may impair the heating of the tumor cells closest to the vessels and may be the site of tumor regrowth or incomplete treatment. This heat-sink effect may also result in dimpling of the treated sphere of tissues next to the vessel. Blood vessels may also be an energy sink as blood conducts energy better than other soft tissue.
The energy at the exposed tip causes ionic agitation and frictional heat, which leads to cell death and coagulation necrosis if hot enough. If the tip is too hot, the vaporization and “charring” may cause decreased energy absorption and less treated tissue volume. In conventional systems, the impedance and temperature at the tip are monitored, and the greater output is adjusted to decrease “charring” and thus increase the volume of tissue treated. The tip temperature, which is measured and used to control the radiofrequency power output, can be significantly lower than the tissue temperature. See, for example, Kongsgaard et al., 1997, PACE 20: 1252-1260; and Haines and Verow, 1990, Circulation 82, 1034-1038, each of which is hereby incorporated by reference in its entirety. If the tip holding the needle electrode is cooled and/or tissue contact is poor, a high RF power output is required to obtain a target temperature. This might lead to overheating, a popping phenomena (Eick et al., 2000, PACE 23, 253-258), and the above-mentioned charring. Active cooling using irrigated ablation catheters has been introduced to increase lesion size. However, this further increases the difference between catheter tip temperature and tissue temperature and eliminates the possibility for feedback control of the radiofrequency power by monitoring catheter tip temperatures.
It is presently believed that some of the hottest tissue spots arise 3-5 mm below the ablation tissue surface. Thus, to prevent charring of tissue, measurement of such hot spots is desirable. With such temperature measurements in hand, the radiofrequency generator output could be adjusted to deliver the greatest level of power that does not result in an increase in electrode temperature beyond a target values such as 80° C. With this and other goals in mind, the present invention provides apparatus and methods for monitoring tissue temperature during RFA or other forms of treatement, such as laser treatment. In some embodiments, the ablation tissue or organ surface is measured using a phosphorescent material. In some embodiments the phosphorescent material is in a catheter and is in optical communication with a light tube within the catheter housing an ablation electrode. In some embodiments, such as dermatological applications, the phosphorescent material can alternatively or additionally be spread on the surface of the tissue or organ to be treated (e.g., spread on the skin). In some embodiments, the phosphorescent material is housed within a needle that punctures the tissue or organ. In such embodiments, the phosphorescent material measures the temperature of the tissue or organ at least 1 to 2 mm away from the tissue or organ surface, for example, 3-5 mm away from the tissue or organ surface. In some embodiments, in addition to or instead of the phosphorescent sensor, an optical tube in the ablation catheter is in optical communication with a pyrometer, thereby sensing infrared wavelengths emitted by the tissue. When properly calibrated, these infrared wavelengths provide an accurate measurement of ablation hot spot temperatures below the surface of the ablation tissue (e.g. 3-5 mm below the ablation tissue surface). In some embodiments, the afore-mentioned phosphorescent sensors are used to calibrate the pyrometer. In some embodiments, rather than using an ablation catheter, a laser is used.
Referring to
Optical fiber medium 88 can communicate with a number of forms of luminescence-based sensors. A form illustrated in
Optical fiber medium 88 can be a bundle of fibers, but is preferably a single optical fiber. Indeed, one of the advantages of the system being described is that very small, single fibers may be extended for a long distance from optical block 11 to luminescence-based sensor 202 (
Analog signal output in line 27 from photodetector 13 is desired to be digitized by an analog-to-digital converter 29 with as few components in between as possible to reduce inherent noise generation and bandwidth restrictions. However, some analog amplification is used in some embodiments so that analog-to-digital converter 29 has enough signal to operate properly. Accordingly, in some embodiments, an input amplifier 31 is utilized, generating in line 33 an amplified version of a time varying signal output of photodetector 13. An exemplary circuit for amplifier 31 is shown in FIG. 5 of U.S. Pat. No. 5,351,268, which is hereby incorporated by reference herein in its entirety.
A digital representation of the amplified photodetector signal is outputted by analog-to-digital converter 29 onto system data bus 35. This is the data bus of signal processor 37. A representative off-the-shelf digital signal processor 37 is part number ADSP2111 of Analog Devices, Inc. This single integrated circuit chip signal processor includes connections for a separate address bus 39 and various peripheral chip control lines 41. Two output ports are provided, one of which is connected to lines 43. Various other output connections are made possible, one of which is attached to conductor 45. This particular signal processor also has connections for interfacing with host computer 72, such as through an interface bus 47. Signal processor 37 appears to host computer 72 as a peripheral device.
Alternatively, if a separate host computer interface 47 is not desired, a less expensive part number ADSP2105 signal processor of Analog Devices, Inc. can be utilized. This latter signal processor does not have provisions for a host interface but a second output port can be engineered into the system, which, unused in the system of
The commercial types of signal processors identified above include a significant amount of random access memory (RAM), enough for the measurement system being described, so external RAM chips are not required. In some embodiments, a programmable read-only memory (PROM) 51 is utilized, however, and is connected to both data bus 35 and address bus 39. In some embodiments, the system operating program is contained within the PROM 51. Signal processor 37 operates, upon power-up, to load the contents of the PROM 51 into its own internal RAM. In some embodiments, signal processor 37 is an application-specific integrated circuit (ASIC) that includes sufficient RAM and logic such that PROM 51 is not necessary. In fact, in some embodiments, DSP 37, PROM 51, digital-to-analog-converter 59, and analog-to-digital converter 29 are all part of a single ASIC chip or ASIC chipset, or equivalents. However, for purposes of describing an exemplary embodiment of the present invention, these components will be considered as if they were discrete logical elements that are not part of an ASIC chip or ASIC chipset.
The system being described operates to excite sensor 202 (or in embodiments in which the fluorescent material is applied directly to the tissue, the fluorescent material by itself) to luminescence by pulsing (e.g., repetitively pulsing) the luminescent material with excitation radiation. In between pulses, characteristics of the decaying luminescence are then measured as an indication of the temperature of tissue or organ 92. Pulsing current is supplied to LED 15 through circuit 53 from power control circuits 55. Power control circuits 55 have two inputs. One is on line 45 from signal processor 37. This line contains a square wave signal that specifies the duration and frequency of the light pulses emitted by LED 15. The intensity of those pulses is controlled by an analog signal in line 57 that is the output of digital-to-analog converter 59. The level of the analog signal in line 57 is set by a digital signal in lines 43 from an output port of signal processor 37. By controlling the intensity output of the pulses of LED 15, the intensity of the resulting luminescent signal returned to photodetector 13 is controlled in order to maintain a substantially uniform signal.
An optional second LED 61 is illustrated as part of optical head 11 and driven by current in line 63 from power control circuits 55. LED 61, if used, is chosen to have a wavelength output that does not excite the luminescent sensor but to which photodiode 13 is sensitive. The purpose of LED 61 is for internal testing of the electronic system. For such testing, it is desired that there be no luminescent signal from the sensor. Power control circuits 55 periodically pulse LED 61 in accordance with the signal in line 45. In some embodiments, digital-to-analog converter 59 is conveniently chosen to be a type with an output 57 that can be driven both positively and negatively by the appropriate digital signal input in lines 43. Power control circuits 55 are then designed to utilize that feature so that a positive going signal in line 57 causes one of LEDs 15 or 61 to be pulsed with an intensity proportional to the value of that signal, while a negative-going pulse causes the other of the LEDs to be energized. Only one of LEDs 15 or 61 is energized at a single time.
Although optical head 11 is designed to minimize the amount of light output of the LED 15 that strikes photodetector 13, it is nearly impossible to prevent all such stray light from reaching the photodetector. Some excitation wavelengths are transmitted back through beam splitter 17. These wavelengths are reflected off the sensor, fiber ends and connectors, and are thus present to some degree in the signal returning to photodetector 13. Although measurement of temperature is made only during intervals between pulses when LED 15 is turned off, it is desirable to avoid driving amplifier circuits 31 to a high level during LED 15 excitation pulses. This is because of the amplifier's power rail saturation recovery time. Therefore, a signal is provided in line 65 to amplifier circuits 31 from attenuator circuit 67. Attenuator 67 receives the same pulse signal in line 45 and intensity level signal in the lines 43 as used to control LED 15. Accordingly, the timing and amount of attenuation of the signal entering amplifier circuits 31 is desirably controlled during the luminescent sensor excitation pulses. As illustrated in
Referring to the waveforms of
The luminescent signal response of the sensor to the excitation signal of
The signal of
The portion of the signal containing the information of temperature or other parameter being measured is decaying portion 73. This is measured after each excitation pulse. A number of such measurements are then averaged to eliminate the effects of noise. The averaged decaying function is then analyzed to measure its characteristic from which the temperature or other parameter is determined.
Referring to
Curve 73 as digitized after passing through the amplifier circuits 31 can be represented as follows:
Ae−at+C (1)
where “C” is an offset signal generated by the photodetector and amplifying circuits 31, “e” is a natural logarithm, “t” is time, “a” is a negative reciprocal of the time constant of the exponentially decaying curve, and “A” is a beginning value of the exponentially decaying signal.
The processing accomplished by signal processor 37 first gathers a large number of sets of digital data taken from the middle of the exponentially decaying signals and combines them into a single signal, as illustrated by the solid portion of the exponential curve of
Ae−at (2)
It is the quantity a, being the negative inverse of the time constant γ, that is desired to be measured. This can be accomplished by signal processor 37 by use of any number of known curve fitting techniques where parameters of an exponential are altered until that exponential matches the composite acquired signal of
LneA+at (3)
Rather than calculating the quantity “a” from a composite set of digital data, it can alternatively be calculated from each set of digital data acquired for one decaying signal and then several of them averaged. This requires a higher calculating speed than is required for the averaging technique described in detail herein but may be desired in certain circumstances.
Operation of the system of
Digital data for one cycle has then been stored. In the case where the data for a number of cycles are combined to provide a single quantity proportional to temperature, this process is repeated a number of times. Step 491 causes the process to repeat the data acquisition cycle just described until it has been done N times. After that, as indicated in step 493, data from N number of cycles is combined by averaging into a single set of data. This composite acquired signal is illustrated in
A next step, in order to simplify calculation of a time constant of this composite signal, is, as indicated at 495, to calculate a natural logarithm of the composite set of data, the results of which are illustrated in
The calculation of parameters of a curve by so-called curve-fitting techniques is well-known. For example, Press et al., Numerical Recipes—The Art of Scientific Computing, Cambridge University Press (1986), pages 498-520 of Chapter 14, which is hereby incorporated by reference, describe such techniques generally and even provide specific computer programs for carrying them out. The curve-fitting techniques initially discussed can be applied directly to the composite set of data formed by step 493, but, as previously mentioned, is a much easier and quicker calculation to do so, in step 497, on a linear set of data that results from the logarithmic calculation of step 495. Step 497 involves calculation of the two constants Lne A and “a” of equation (3) given above, as illustrated in
The calculated beginning point of the decaying curve, Lne A, is calculated so that it may be used in an optional step 499. This is a quantity that is not measured since no data are acquired from the decaying intensity curve immediately at the end of an excitation pulse in typical embodiments. If there are known changes in operation of the system, such as a sudden increase in the intensity of the excitation light from LED 15, the quantity “Lne A” can be monitored to see if it appropriately changes in a next cycle. This quantity is independent of the temperature or other parameter being measured. But if it is detected that this quantity does not change as might be expected, such as by suddenly increasing the intensity of LED 15, then it will be known that the composite data just acquired and analyzed is likely not accurate. Such a circumstance could indicate that amplifier 31 has been driven into saturation.
In such a case, the data will be rejected and the processing commenced again with step 483. However, if no problem is detected with the data, the value of the quantity “a” is used to calculate temperature, as indicated in a step 501. The quantity a can be converted directly to temperature, for example, by use of a look-up table for the particular luminescent material being utilized as a temperature sensor.
In order to maintain the signal levels in photodetector 13 and amplifier 31 as high as possible without operating them in saturation or other non-linear operating range, the intensity of LED 15 excitation pulses is controlled as part of a feedback loop from the output. As previously mentioned, the digital-to-analog converter of
In order to determine whether the output signal level is within range or not, the absolute value of one region of the composite acquired signal curve of
A final step 507 in the processing of
Even with amplifier 31 being designed to have ample bandwidth, some high frequency components of an initial portion of the luminescent intensity curve are attenuated and not amplified by it. This is a reason for the delay described with respect to
Details of components for measuring tissue temperature using a quantity of luminescent material have been described in conjunction with
In the embodiment shown in
In some embodiments, energy generator 74 delivers power to an ablation electrode 204 (
In some embodiments, energy generator 74 is a laser that delivers power to a laser probe (not shown) via coupling 84. In some embodiments, energy generator 74 is a laser generator that delivers a pulse frequency between 2 Hz and 40 k Hz or a continuous laser pulse to a laser probe (not shown). Exemplary laser probes include, but are not limited to, (i) LED clusters for superficial treatments over large areas (e.g., wound healing); (ii) infra-red single laser probes for pain relieve and deep musculoskeletal disorders (e.g., joint, tendon, bone); (iii) infrared laser clusters for pain relief and deep musculoskeletal disorders over large areas; (iv) visible red single laser probes for wound healing and dermatology, and (v) visible red laser clusters for wound healing and dermatology over large areas. In embodiments where a laser probe is used, connection 86 is not required.
In typical embodiments, the subject having tissue or organ 92 to be treated is a human. However, the present application is not limited to humans. Any subject having tissue in need of radiofrequency ablation or laser therapy can benefit from the systems and methods of the present invention. Moreover, the systems and methods of the present invention have wide applicability in the research setting (e.g., to identify improved radiofrequency ablation techniques using research animals or tissue obtain from research animals).
In some embodiments, in addition to the core components, the system comprises a pyrometer 76 for measuring infrared wavelengths given off by tissue or organ 92. An example of a suitable pyrometer 76 is a PhotriX OEM pyrometer (Luxtron, Santa Clara, Calif.) using, for example, lightpipe optics. In some embodiments, pyrometer 76 is an InxGa1-xAs pyrometer where x is a positive number less than 1 (e.g., 0.74, 0.82, etc.). In some embodiments, pyrometer 76 has a long wavelength cutoff of 1.68 μm. In some embodiments, pyrometer 76 is responsive to wavelengths in the range of about 0.9 μm to about 1.9 μm. In some embodiments, pyrometer 76 is responsive to wavelengths in the range of about 1.0 μm to about 2.2 μm. In some embodiments, pyrometer 76 is responsive to wavelengths in the range of about 1.2 μm to about 2.6 μm. Pyrometer 76 can measure temperatures over a broad range. For example, in some embodiments, pyrometer 76 can measure accurate temperature values in the temperature ranges that arise in tissue or organ 92 during treatment (e.g. 30° C. to 105° C.).
Pyrometer 76 is coupled to a site on tissue or organ 92 by connection 100. In some embodiments, connection 100 is a light pipe.
Now that an overview of the invention has been given, specific embodiments will be described. One embodiment of the present invention provides a laser ablation system in accordance with
Now referring to
Now referring to
In some embodiments, rather than measuring time decay, the system illustrated in
Energy generators 74 that are RF-generators have been described. However, the present invention is not limited to RF-generators. Indeed, any energy source suitable for electrosurgery and laser therapy, and more particularly for use with surgical and cosmetic methods that use energy to resect, coagulate, or ablate tissue or organs, is within the scope of the present invention and may serve the purpose of energy generator 74 in
In some embodiments, tissue or organ 92 is any association of cells of a multicellular organism, with a common embryological origin or pathway and similar structure and function. Often, cells of a tissue or organ 92 are contiguous at cell membranes. In the present invention, tissues are generally solid rather than liquid (e.g. blood). However, in some embodiments, the tissue is liquid. Cells in tissue 92 may be all of one type (a simple tissue, e.g. squamous epithelium) or of more than one type (a mixed tissue, e.g., connective tissue). Tissues aggregate to form organs. Thus, in some embodiments, tissue 92 is in fact an organ. An organ is a functional and anatomical unit of most multicellular organisms, consisting of at least two tissue types (often several) integrated in such a way as to perform one or more recognizable functions in the organism. Examples in animals include liver, kidney and skin. Additional examples of tissue or organ 92 include, but are not limited to heart, bladder, lung, liver, muscle, salivary gland, colon, spleen, pancreas, gallbladder, liver, kidney, stomach, tongue, thyroid gland, gallbladder, brain, large intestine, and small intestine.
Suitable luminescent materials that emit in two different wavelength ranges. The fundamental characteristics of one form of phosphor material for use in the present invention is that when properly excited it emits radiation in at least two different wavelength ranges that are optically isolatable from one another, and further that the intensity variations of the radiation within each of these at least two wavelength ranges as a function of the phosphor temperature are known and different from one another. A phosphor material is preferred that is further characterized by its radiation emission in each of these at least two wavelength bands being sharp lines that rise from substantially zero emission on either side to a maximum line intensity, all in less than 100 angstroms. The lines are easy to isolate and have their own defined bandwidth. But mixtures of broadband emitters, such as of more conventional non-rare earth phosphors, are also usable so long as two different wavelength ranges of emission of the two materials can be separated sufficiently from one another so that an intensity ratio can be taken, and as long as the temperature dependences for thermal quenching are sufficiently different for the two phosphors.
For a practical temperature measuring device, the phosphor material selected should also emit radiation in the visible or near visible region of the spectrum since this is the easiest radiation to detect with available detectors, and since radiation in this region is readily transmitted by glass or quartz windows, fibers, lenses, etc. It is also desirable that the phosphor material selected be an efficient emitter of such radiation in response to some useful and practical form of excitation of the phosphor material. The particular phosphor material or mixture of phosphor materials is also desirably chosen so that the relative change of intensity of emission of radiation within the two wavelength ranges is a maximum within the temperature range to be measured. The phosphor material should also be durable, stable and be capable of reproducing essentially the same results from batch to batch. In the case of fiber optic transmission of the phosphor emission, as described in specific embodiments hereinafter, a sharp line emitting phosphor is desirably selected with the lines having wavelengths near one another so that any wavelength dependent attenuation of the fiber optic will not significantly affect the measured results at a position remote from the phosphor, thereby eliminating or reducing the necessity for intensity compensation that might be necessary if fibers of varying lengths were used.
The composition of a phosphor material capable of providing the characteristics outlined above may be represented very generally by the generic chemical compound description AxByCz, where A represents one or more cations, B represents one or more anions, A and B together form an appropriate non-metallic host compound, and C represents one or more activator elements that are compatible with the host material. Here, x and y are small integers and z is typically in the range of a few hundredths or less.
There is a large number of known existing phosphor compounds from which those satisfying the fundamental characteristic discussed above may be selected. A preferred group of elements from which the activator element C is chosen is any of the rare earth ions having an unfilled f-electron shell, all of which have sharp isolatable fluorescent emission lines of 10 angstroms bandwidth or less. Certain of these rare earth ions having comparatively strong visible or near visible emission are preferred for convenience of detecting, and they are typically in the trivalent form: praseodymium (Pr), samarium (Sm), europium (Eu), terbium (Th), dysprosium (Dy), holmium (Ho), erbium (Er) and thulium (Tm). Other activators such as neodymium (Nd) and ytterbium (Yb) might also be useful if infra-red sensitive detectors are used. Other non-rare earth activators having a characteristic of sharp line emission which might be potentially useful in the present invention would include uranium (U) and chromium (Cr3+). The activator ion is combined with a compatible host material with a concentration of something less than 10 atom percent relative to the other cations present, and more usually less than 1 atom percent, depending on the particular activator elements and host compounds chosen.
A specific class of compositions that might be included in the phosphor layer is a rare earth phosphor having the composition (RE)2O2S:X, wherein RE is one element selected from the group consisting of lanthanum (La), gadolinium (Gd) and yttrium (Y), and X is one doping element selected from the group of rare earth elements listed in the preceding paragraph having a concentration in the range of 0.01 to 10.0 atom percent as a substitute for the RE element. A more usual portion of that concentration range will be a few atom percent and in some cases less than 0.1 atom percent. The concentration is selected for the particular emission characteristics desired for a given application. Such a phosphor compound may be suspended in an organic binder, a silicone resin binder or a potassium silicate binder. Certain of these binders may be the vehicle for a paint which can be maintained in a liquid state until thinly spread over a surface whose temperature is to be measured where it will dry and thus hold the phosphor on the surface in heat conductive contact with it.
A specific example of such a material is europium-doped lanthanum oxysulfide (La2O2S:Eu) where europium is present in the range of a few atom percent down to 0.01 atom percent as a substitute for lanthanum. More information on phosphors suitable with this embodiment of the present invention is provided in U.S. Pat. No. 4,560,286, which is hereby incorporated by reference in its entirety.
Suitable luminescent materials that emit with a decay time as a function of temperature. Many specific luminescent material compositions can be utilized for the sensor in the system being described in accordance with this embodiment of the invention. The material must be stable over time and up to temperatures in excess of those to be measured. The chosen luminescent composition also needs to be strongly absorptive of the radiation output of available LEDs, and emit luminescent radiation in wavelength ranges to which available high bandwidth (fast responding) photodetectors are available. The luminescent sensor composition chosen should also be easily reproducible in order to reduce variations in characteristics between different sensors. The luminescent material preferably has a decay time constant in a range of from one microsecond to one millisecond. Within this range, the requirements placed on the electronic system are not too severe, yet repeated measurements can still be made with a sufficiently high rate.
An exemplary luminescent material used in some embodiments is a chromium-activated yttrium gallium garnet having a specific composition Y3(Ga1-xCrx+3)5O12, where X lies substantially within a range of 0.032 to 0.078, representing a concentration of the trivalent chromium activator of from 2.0 to 4.5 percent by weight.
An advantage of the opto-electronic system described above is that it can work with a luminescent material having a short decay time. The preferred material whose characteristics are illustrated in
Another specific luminescent material that is suitable is a trivalent chromium doped yttrium aluminum garnet, having a chemical formula of Y3(Al1-xCrx+3)5O12, where x lies within a range of 0.16 to 0.060, representing a concentration of trivalent chromium dopant of from one to four percent by weight. This material has a luminescence that is less bright than that of Y3(Ga1-xCrx+3)5O12, and has a much longer time constant. Its excitation, absorption and luminescent spectra are, however, quite similar.
Trivalent chromium doped rare earth aluminum borate materials can also be used. Found to have excitation, absorption and luminescent emission spectra similar to the preferred material described above, and with the same or greater luminescent brightness, and with a shorter decay time constant, are certain yttrium aluminum, gadolinium aluminum and lutetium aluminum borates. Examples are chemical compositions Gd(Al1-xCrx+3)3(BO3)4 and Lu(Al1-xCrx+3)3(BO3)4, where x is generally in the range of from 0.01 to 0.04. More information on phosphors suitable with this embodiment of the present invention is provided in U.S. Pat. No. 5,351,268, which is hereby incorporated by reference in its entirety.
In some embodiments, energy generator 74 generates a pulsed laser. In other embodiments, energy generator 74 generates a laser beam that irradiates continuous energy. In some embodiments, a pulsed laser used in the present invention has a pulse frequency in the range of 0.1 kilohertz (kHz) to 1000 kHz. In some embodiments, a pulsed laser has a pulse duration in the range of 10 nanoseconds to 3.0×107 nanoseconds. In some embodiments, energy generator 74 and an associated laser probe is a gas, liquid, or solid laser. Exemplary gas lasers include, but are not limited to, He—Ne, He—Cd, Cu vapor, Ag vapor, HeAg, NeCu, CO2, N2, HF-DF, far infrared, F2, XeF, XeCl, ArF, KrCl, or KrF laser. Exemplary liquid lasers include dye lasers. Exemplary solid lasers include, but are not limited to, ruby, Nd:YAG, Nd:glass, color center, alexandrite, Ti:sapphire, Yb:KGW, Yb:KYW, Yb:SYS, Yb:BOYS, Yb:CaF2, semiconductor, glass or optical fiber hosted lasers, vertical cavity surface-emitting laser (VCSEL), or laser diode laser. In some embodiments, a laser beam is generated by an x-ray, infrared, ultraviolet, or free electron transfer laser. In some embodiments, a laser beam has a wavelength in the range of 10 nanometers to 1×106 nanometers. In some embodiments, a dose of radiant energy containing radiant energy in a range from 0.01 Joules per square centimeters (J/cm2) to 50.0 J/cm2 is delivered to a designated area by a laser beam.
All references cited herein are incorporated herein by reference in their entirety and for all purposes to the same extent as if each individual publication or patent or patent application was specifically and individually indicated to be incorporated by reference in its entirety for all purposes.
Many modifications and variations of this invention can be made without departing from its spirit and scope, as will be apparent to those skilled in the art. The specific embodiments described herein are offered by way of example only, and the invention is to be limited only by the terms of the appended claims, along with the full scope of equivalents to which such claims are entitled.
